NMNH: 1. “Bonzyme” Whole-enzymatic method, environmental-friendly, no harmful solvent residues manufacturing powder. 2. Bontac is a very first manufacture in the world to produce the NMNH powder on the level of high purity, stability. 3. Exclusive “Bonpure” seven-step purification technology, high purity(up to 99%) and stability of production of NMNH powder 4. Self-owned factories and obtained a number of international certifications to ensure high quality and stable supply of products of NMNH powder 5. Provide one-stop product solution customization service
NADH: 1. Bonzyme whole-enzymatic method, environmental-friendly, no harmful solvent residues 2. Exclusive Bonpure seven-step purification technology, purity up higher than 98 % 3. Special patented process crystal form, higher stability 4. Obtained a number of international certifications to ensure high quality 5. 8 domestic and foreign NADH patents, leading the industry 6. Provide one-stop product solution customization service
NAD: 1. “Bonzyme” Whole-enzymatic method, environmental-friendly, no harmful solvent residues 2. Stable supplier of 1000+ enterprises around the world 3. Unique “Bonpure” seven-step purification technology, higher product content and higher conversion rate 4. Freeze drying technology to ensure stable product quality 5. Unique crystal technology, higher product solubility 6. Self-owned factories and obtained a number of international certifications to ensure high quality and stable supply of products
NMN: 1. “Bonzyme”Whole-enzymatic method, environmental-friendly, no harmful solvent residues 2. Exclusive“Bonpure”seven-step purification technology, high purity(up to 99.9%) and stability 3. Industrial leading technology: 15 domestic and international NMN patents 4. Self-owned factories and obtained a number of international certifications to ensure high quality and stable supply of products 5. Multiple in vivo studies show that Bontac NMN is safe and effective 6. Provide one-stop product solution customization service 7. NMN raw material supplier of famous David Sinclair team of Harvard University
Bontac Bio-Engineering (Shenzhen) Co., Ltd. (hereafter referred to as BONTAC) is a high-tech enterprise established in July 2012. BONTAC integrates R&D, production and sales, with enzyme catalysis technology as the core and coenzyme and natural products as main products. There are six major series of products in BONTAC, involving coenzymes, natural products, sugar substitutes, cosmetics, dietary supplements and medical intermediates.
As the leader of the global NMN industry, BONTAC has the first whole-enzyme catalysis technology in China. Our coenzyme products are widely used in health industry, medical & beauty, green agriculture, biomedicine and other fields. BONTAC adheres to independent innovation, with more than 170 invention patents. Different from the traditional chemical synthesis and fermentation industry, BONTAC has advantages of green low-carbon and high-value-added biosynthesis technology. What’s more, BONTAC has established the first coenzyme engineering technology research center at the provincial level in China which also is the sole in Guangdong Province.
In the future, BONTAC will focus on its advantages of green, low-carbon and high-value-added biosynthesis technology, and build ecological relationship with academia as well as upstream/downstream partners, continuously leading the synthetic biological industry and creating a better life for human beings.
NMN was only considered as a source of cellular energy and an intermediate in NAD+ biosynthesis, currently, the attention of the scientific community has been paid on anti-aging activity and a variety of health benefits and pharmacological activities of NMN which are related to the restoring of NAD+. Thus, NMN has therapeutic effects towards a range of diseases, including age-induced type 2 diabetes, obesity, cerebral and cardiac ischemia, heart failure and cardiomyopathies, Alzheimer’s disease and other neurodegenerative disorders, corneal injury, macular degeneration and retinal degeneration, acute kidney injury and alcoholic liver disease.
NMN powder in general is typically produced via chemical or enzymatic synthesis, or fermentation biosynthesis. There are pros and cons to all three methods.
Chemical synthesis is expensive and labor intensive, and all raw ingredients used are categorized as “unnatural,” i.e., not from biological systems. There are, however, some advantages from the manufacturer’s perspective. The yield is well suited to mass NMN powder production, and all of those unnatural raw ingredients can be carefully controlled. But there are a number of drawbacks as well. Some of the solvents used in the manufacturing process are seriously bad from an environmental standpoint, and impurities and by-products can be challenging to remove from the finished product – that’s seriously bad for the consumer.
Enzymatic production of NMN powder, on the other hand, is considered a “green preparation method.” Like the chemical route, it’s pricey, but it offers a higher yield and impressively high purity. The finished NMN ticks all the boxes – stable, easily absorbed, lightweight, low density, and a low molecular structure.
Fermentation has also been explored as a method of producing NMN, but yield, though high quality, is pretty abysmal, so many supplement companies quite sensibly look to other, more efficacious processes.
1、“Bonzyme”Whole-enzymatic method, environmental-friendly, no harmful solvent residues manufacturing powder
2、Exclusive“Bonpure”seven-step purification technology, high purity(up to 99.9%) and stability of production of NMN powder
3、Industrial leading technology: 15 domestic and international NMN patents
4、Self-owned factories and obtained a number of international certifications to ensure high quality and stable supply of products of NMN powder
5、Multiple in vivo studies show that Bontac NMN powder is safe and effective
6、Provide one-stop product solution customization service
7、NMN raw material supplier of famous David Sinclair team of Harvard University.
Aging, as a natural process is identified by downregulation of energy production in mitochondria of various organs such as brain, adipose tissue, skin, liver, skeletal muscle and pancreas due to the depletion of NAD+ . NAD+ levels in the body decrease as a consequence of increasing NAD+ consuming enzymes when aging There are three different biosynthesis pathways to produce NAD+ in mammalian cells including de novo synthesis from tryptophan, salt and Preiss-Handler pathways. Among these three pathways, NMN is an interproduct by is involved in NAD+ biosynthesis through salt and Preiss-Handler pathways. The salvage pathway is the most efficient and the main route for the NAD+ biosynthesis, in which nicotinamide and 5-phosphoribosyl-1-pyrophosphate are converted to NMN with the enzyme of NAMPT followed by conjugation to ATP and conversion to NAD by NMNAT. Furthermore, NAD+ consuming enzymes are responsible for degradation of NAD+ and consequence nt formation of nicotinamide as a by-product.
The safety of NMN powder cannot be assessed since required clinical and toxicological studies have not been completed yet to establish the recommended safe levels for long term administration. Nevertheless, their safety and efficacy are uncertain and unreliable since most of them have not been back by Rigorous scientific preclinical and clinical testing. This issue has been arisen as manufacturers are hesitant to pay for research and clinical trials due to potential lower profit margin, and there is no authorizing agency to regulate NMN products because it is often product sold as functional food than heavily regulated therapeutic drug. Therefore, more strict approval process has been demanded by consumer advocacy groups requesting regulatory agencies to set standard and restrictions for marketing anti-aging health products, considering safety, health and wellbeing of N red besumers. a panacea for the elderly, because boosting NAD levels when not required may yield some detrimental effects. Therefore, the dose and frequency of NMN supplementation should be carefully prescribed depending on the type of age-related deficiency and all other confronting health conditions of the people. Other NAD precursors over have been studied to diverse age-related deficiencies and they are used for particular deficiencies, only after they are proven for effectiveness and safe to use. Therefore, the same principle should be applied to NMN as well
First, inspect the factory. After some screening, NMN companied that directly face consumers pay more attention to brand building. Therefore, for a good brand, quality is the most important thing, and the first thing to control the quality of raw materials is to inspect the factory. Bontac company actually manufacturing NMN powder of high quality with the caterias of SGS. Secondly, the purity is tested. Purity is one of the most important parameters of NMN powder. If high purity NMN cannot be guaranteed, the remaining substances are likely to exceed the relevant standards. As the attached certificates demonstrates that the NMN powder produced by Bontac reach the purity of 99.9%. Finally, a professional test spectrum is needed to prove it. Magnetic Resonance Spectroscopy (NMR) and high-resolution mass spectrometry (HRMS). Usually through the analysis of these two spectra, the structure of the compound ca n be preliminarily determined.
Introduction Wound healing is a sophisticated process responding to tissue damage, which is associated with numbers of interaction of various cell types, cytokines, growth factors, and other molecules. Strikingly, increasing the nicotinamide adenine dinucleotide (NAD) pool by nicotinamide riboside (NR) can accelerate wound healing and macrophage migration, which is partially achieved through PGE2 synthesis and signaling as well as the function of the NAD+-dependent sirtuin, SIRT3. Regulatory effects of NR on the expression of M1 macrophage markers in human MDMs. NR could modulate the expression levels of canonical M1 (inflammatory phenotype) and M2 (reparative phenotype) cell surface markers during macrophage polarization. With a great detail, a significant downregulation in CD64 and a obvious upregulation of CD197/CCR7 are viewed in the polarized M1 cells incubated with NR. Furthermore, NR increases CD197/CCR7-mediated M1 macrophage migration. The significance of chemotaxis mediator PGE2 in NR-regulated macrophage migration NR-mediated upregulation of macrophage migration through CCL19/CCR7 is dependent on the synthesis of PGE2, an inflammatory lipid mediator in the eicosanoid family. Concretely, NR administration increases the PGE2 level in cultured human monocytes, MDMs, and human serum. In addition, NR-mediated increases in CCR7 expression and CCL19-induced migration are attenuated by PGE2 synthesis blockers. NR/SIRT3/migration axis in human M1 MDMs NR facilitates collective cell migration at a SIRT3-dependent manner in human M1 MDMs during wound healing. Simply put, the degree of wound healing is compared on Day 0 and Day 2 in vehicle- or NR-treated human M1 MDMs. It is found that NR increases the relative degree of migration (relative wound healing) and the rate of wound confluence in the presence of CCL19. Besides, the relative degree of wound density (migration) is blunted by SIRT3 knockdown, while being enhanced by SIRT3 overexpression. Application prospect of NR in wound healing Chronic diabetes is often accompanied with poor wound healing. For instance, diabetic foot ulcers, one of the chief cause of amputations, affect 15% of people with diabetes. Given that NR can drive the macrophage migration to boost chronic wound healing, it may have a broad application prospect in treating the wounds including but not limited to diabetic patients. Conclusion In human macrophages, NR induces surface expression of the chemotaxis CD197/CCR7 receptor and levels of its lipid mediator PGE2 via upregulation of cyclooxygenase 2 and functionally increases macrophage migration and wound healing in a SIRT3-dependent manner. Reference Wu J, Bley M, Steans RS, et al. Nicotinamide Riboside Augments Human Macrophage Migration via SIRT3-Mediated Prostaglandin E2 Signaling. Cells. 2024;13(5):455. Published 2024 Mar 5. doi:10.3390/cells13050455 BONTAC NR BONTAC is one of the few suppliers in China that can launch mass production of raw materials for NR, with self-owned factory and professional R&D team. Up till now, there are 173 BONTAC patents. BONTAC provides one-stop service for customized products. Both malate and chloride salt forms of NR are available. By dirt of unique Bonpure seven-step purification technology and Bonzyme Whole-enzymatic method, the product content and conversion rate can be maintained in a higher level. The purity of BONTAC NR can reach above 97%. Our products are subjected to strict third-party self-inspection, which are worth of trustworthy. Disclaimer This article is based on the reference in the academic journal. The relevant information is provided for sharing and learning purposes only, and does not represent any medical advice purposes. If there is any infringement, please contact the author for deletion. The views expressed in this article do not represent the position of BONTAC. Under no circumstances will BONTAC be held responsible or liable in any way for any claims, damages, losses, expenses, costs or liabilities whatsoever (including, without limitation, any direct or indirect damages for loss of profits, business interruption or loss of information) resulting or arising directly or indirectly from your reliance on the information and material on this website.
Introduction Mar 4th is determined as the World Obesity Day. World Obesity Federation, UNICEF and WHO have hosted a global youth-led webinar to talk about obesity & youth. The obesity crisis has gradually attracted much attention. The latest report by the Lancet suggests that one billion people are bothered by obesity (2022), with 650 million adults, 340 million adolescents and 39 million children. Recently, etiological studies and interventions for obesity have been progressively focused on the central nervous system, with an attempt to curb the onset of obesity at its source. Notably, targeting NAD+ salvage pathway in hypothalamic astrocytes may be a potential approach to combat obesity. The association of hypothalamic astrocytes and obesity The hypothalamus functions as the appetite regulation center, which receives and integrates the neuroendocrine factors produced by the central nervous system and peripheral tissues to promote or suppress appetite, so as to affect body weight. Noteworthily, aypothalamic astrocytes can apparently decrease glucose clearance and increase plasma insulin levels, playing an essential role in modulating energy metabolism, which are expected to be a new target for obesity treatment. Alleviation of high-fat diet (HFD)-induced obesity by repressing astrocyte NAD+ salvage pathway Under conditions of excessive fat intake, the NAD+ salvage pathway is specifically activated in hypothalamic astrocytes, which restrains the energy expenditure (EE) and fat oxidation in adipose tissues by downregulating sympathetic nerve innervation, eventually resulting in the accumulation of adipose tissue fat and the development of obesity. CD38 as a downstream mediator of astrocyte inflammation induced by the NAD+ salvage pathway. CD38 functions downstream of the NAD+ salvage pathway in hypothalamic astrocytes burdened with excess fat. CD38 knockdown in arcuate nucleus astrocytes diminishes the weight gain, reduces fat mass, increases EE, and lowers RER during HFD consumption. Cd38 depletion in hypothalamic astrocytes may improve hypothalamic inflammation by increasing NAD+ level. Hypothalamic inflammation can not only lead to energy imbalances, but also exacerbate central insulin resistance and leptin resistance, which can lead to the accumulation of fat in peripheral tissues. The role of nicotinamide phosphoribosyltransferase (NAMPT)–NAD+–CD38 axis in obesity In mammals, the salvage pathway represents the primary means of maintaining cellular NAD+ level. A crucial step in the NAD+ salvage pathway is catalyzed by NAMPT. In response to fat overload, the activation of the astrocytic NAMPT-NAD+-CD38 axis induces pro-inflammatory responses in the hypothalamus, eliciting aberrantly activated basal Ca2+ signals and compromised Ca2+ responses to metabolic hormones such as insulin, leptin, and glucagon-like peptide 1, ultimately resulting in dysfunctional hypothalamic astrocytes and contribute to the development of obesity. Conclusion Mechanically, inhibition of hypothalamic astrocytic NAD+ salvage pathway, along with its downstream CD38, mitigates hypothalamic inflammation and attenuates the development of HFD-induced obesity in male mice. Reference Park, J.W., Park, S.E., Koh, W. et al (2024). Hypothalamic astrocyte NAD+ salvage pathway mediates the coupling of dietary fat overconsumption in a mouse model of obesity. Nat Commun 15, 2102. https://doi.org/10.1038/s41467-024-46009-0 BONTAC NAD BONTAC has been dedicated to the R&D, manufacture and sale of raw materials for coenzyme and natural products since 2012, with self-owned factories, over 170 global patents as well as strong R&D team. BONTAC has rich R&D experience and advanced technology in the biosynthesis of NAD and its precursors (eg. NMN and NR). There are various types of NAD to be selected, encompassing NAD ER Grade (endoxin removal), NAD Grade I (IVD/dietary supplement/cosmetics raw powder), NAD Grade II (API/intermediates) and NAD Grade IV (if any higher requirement on the solubility), which can be provided in the form of lyophilized powder or crystalline powder. The purity of BONTAC NAD can reach above 98%. Disclaimer This article is based on the reference in the academic journal. The relevant information is provided for sharing and learning purposes only, and does not represent any medical advice purposes. If there is any infringement, please contact the author for deletion. The views expressed in this article do not represent the position of BONTAC. BONTAC holds no responsibility for any claims, damages, losses, expenses or costs resulting or arising directly or indirectly from your reliance on the information and material on this website.
1. Introduction Nicotinamide mononucleotide (NMN) supplementation has been suggested to hamper the inflammatory responses via restoring NAD+ level and downregulating the expression of Cyclooxygenase-2 (COX-2). Strikingly, both Aryl hydrocarbon receptor (AhR) and Indoleamine 2,3-Dioxygenase 1 (IDO1), two key enzymes for kynurenine production, can mediate the anti-inflammatory function of NMN in RAW 264.7 macrophages. 2. The alleviated inflammatory response in the presence of NMN supplementation For deciphering the impact of NMN in vivo, mice are subjected to daily intraperitoneal (i.p.) injection of NMN (500 mg/kg) for consecutive 6 days, followed by i.p. injection of lipopolysaccharides (LPS) (5 mg/kg) or alum (700 μg) on day 7. It is discovered that NMN supplementation suppresses LPS- or alum-induced inflammation in mice, as manifested by the downregulation of proinflammatory cytokines (IL-6 and IL-1β) and proinflammatory enzyme (COX-2). 3. The necessity of AhR for NMN-mediated inhibition of inflammatory response in macrophages AhR, a ligand-activated transcription factor, can mediate the anti-inflammatory function of NMN upon LPS treatment in RAW264.7 cells. Specifically, NMN reduces the expression of COX-2 in cells in bearing AHR. On the contrary. AhR inhibitor (CH223191) deprives the downregulation of IL-6, IL-1β and COX-2 caused by NMN treatment. Likewise, NMN treatment fails to reduce the expression levels of IL-6, IL-1β, and COX-2 in AhR knockout cells. 4. The importance of IDO1/kynurenine/AhR axis in the anti-inflammation function of NMN IDO1 is the rate-limiting enzyme in tryptophan catabolism to produce kynurenine, a metabolic intermediate in NAD+ de novo synthesis pathway. Kynurenine can promote the translocation of AhR from the cytoplasm to nucleus, thereby exerting an anti-inflammatory effect. NMN inhibits LPS-induced inflammation in a IDO1-kynurenine dependent manner in macrophages. 5. Conclusion NMN supplementation mitigates COX-2-associated inflammatory responses by activating lDO-kynurenine-AhR pathway, providing new insights into NAD* regulation in macrophage activation. Reference Liu J, Hou W, Zong Z, et al. Supplementation of nicotinamide mononucleotide diminishes COX-2 associated inflammatory responses in macrophages by activating kynurenine/AhR signaling. Free Radic Biol Med. Published online February 8, 2024. doi:10.1016/j.freeradbiomed.2024.01.046 BONTAC NMN BONTAC is the pioneer of NMN industry and the first manufacturer to launch NMN mass production, with the first whole-enzyme catalysis technology around the world. At present, BONTAC has become the leading enterprise in niche areas of coenzyme products. Notably, BONTAC is the NMN raw material supplier of famous David Sinclair team at the Harvard University, who uses the raw materials of BONTAC in a paper titled “Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging”. Our services and products have been highly recognized by global partners. Furthermore, BONTAC has the first national and the only provincial independent coenzyme engineering technology research center in Guangdong, China. The coenzyme products of BOMNTAC are widely used in fields such as nutritional health, biomedicine, medical beauty, daily chemicals and green agriculture. Disclaimer This article is based on the reference in the academic journal. The relevant information is provide for sharing and learning purposes only, and does not represent any medical advice purposes. If there is any infringement, please contact the author for deletion. The views expressed in this article do not represent the position of BONTAC. Under no circumstances will BONTAC be held responsible or liable in any way for any claims, damages, losses, expenses, costs or liabilities whatsoever (including, without limitation, any direct or indirect damages for loss of profits, business interruption or loss of information) resulting or arising directly or indirectly from your reliance on the information and material on this website.